HBV Drugs Cut Risk of Cancer Recurrence

by Michael Smith Michael Smith North American Correspondent, MedPage Today
November 12, 2012

Action Points

The rate of long-term disease-free survival after liver resection remains suboptimal due to persistent high incidences of hepatocellular carcinoma recurrence.

In this retrospective study, the authors found that nucleoside analog use was associated with a lower risk of hepatocellular carcinoma recurrence among patients with HBV-related disease after liver resection.

In a nationwide cohort from Taiwan, 20.5% of patients treated with anti-HBV nucleoside analogs had recurrence of their cancer, according to Chun-Ying Wu, MD, PhD, of National Yang-Ming University in Taipei.

In contrast, those who did not get the drugs – entecavir (Baraclude), lamivudine (3TC), and telbivudine (Tyzeka) – had a recurrence rate of 43.6%, Wu reported at the annual meeting of the American Association for the Study of Liver Diseases and online in the Journal of the American Medical Association.

Previous research into the issue has been limited and has yielded conflicting results, Wu noted.

To help settle the question, Wu and colleagues turned to the national health system of Taiwan, which includes 99% of the population, as well as to databases covering reimbursement for nucleoside analogs and mortality.

From October 2003 to September 2010, they identified 4,569 patients who had HBV-related hepatocellular carcinoma and received curative surgery. Of those, they reported, 518 were given nucleoside analogs for an average of 1.45 years.

Aside from the lower risk of recurrence, which was significant at P<0.001, they found:

After adjusting for competing mortality, the treated cohort had a lower 6-year recurrence rate -- 45.6% compared with 54.6% (P<0.001)

Overall, after 6 years, 29% of the treated cohort and 42.4% of the untreated cohort had died of any cause (P<0.001)

In a modified Cox regression analysis, using nucleoside analogs was associated with a 33% reduction in cancer risk (HR 0.67, 95% CI 0.55 to 0.81, P<0.001)

The use of statins and nonsteroidal anti-inflammatory drugs or aspirin was also independently associated with a lower cancer risk

The researchers cautioned that the study was observational and cannot pin down cause and effect. They also noted that they were unable to account for patients who purchased their own drugs and were not reimbursed or for those who were prescribed the drugs but had poor compliance.

The study has several strengths, including its large size and completeness, commented Anna Lok, MD, of the University of Michigan in Ann Arbor.

But despite that, the findings "are by no means definitive enough to answer the question of whether antiviral therapy after curative resection of hepatitis B-related (hepatocellular carcinoma) will prevent disease recurrence."

Among other issues, Lok wrote in an accompanying editorial in the journal, the researchers started their follow-up periods at different times – immediately after release for the untreated cohort and at first drug prescription on the treated patients.

But the latter period began, on average, more than a year after surgery, Lok noted, which would have excluded early recurrences and therefore likely amplified the observed benefit.

"It is unrealistic," Lok added, to expect that 1 or 2 years of antiviral therapy can prevent recurrence, especially since early recurrences are likely a result of previously undiscovered metastasis from the primary tumor.

The study was supported by Taiwan's National Health Research Institute. The journal said the authors reported no conflicts.

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